The lung cancer early detection CVC has two main goals: Specific Aim 1 is to develop a bloodbased biomarker panel for personalized risk assessment, modeled for its cost effectiveness. To this effect, substantial validation work in phase 3 studies has been done using retrospective longitudinal cohorts to test the performance of a four-marker protein panel (4MP) as a means to determine lung cancer risk and need for CT screening. The goal moving forward is to test the 4MP alone and in combinations with other types of markers in the screening setting, using lung cancer screening cohorts available to the CVC. The resulting marker panel, in combination with subject characteristics, would identify subjects who are currently not eligible based on USPSTF criteria that would benefit from CT screening based on their risk, ultimately leading to a utility trial for which a concept has been presented at a recent EDRN scientific meeting. The utility trial concept also includes as an objective to test the value of biomarkers in informing subjects who are currently eligible but not decided to undergo CT screening, about their risk through a decision sharing process. Specific Aim 2 will test the use of biomarkers and AI for interpretation of CT images and to personalize the screening frequency and duration. Sub Aim 1 is intended to validate the macrovasculature surrounding a nodule (vessel number) previously developed as a biomarker, in an independent screening cohort. Sub Aim 2 is intended to develop a validated integrative computational model for improved early lung cancer detection that includes bloodbased biomarkers, CT features such as emphysema, presence or absence of a nodule, small airways and subject characteristics for interpretation of CT images and to determine screening frequency. The model will be subjected to a cost effectiveness analysis compared to current lung cancer screening guidelines. The CVC represents a multi-institution, multi-investigator effort with expertise in cancer biomarkers and statistics; pulmonology and lung cancer; epidemiology; radiomics, bioinformatics and artificial intelligence; and clinical trial design, simulation modeling and cost-effectiveness analysis. The CVC brings in substantial accomplishments in biomarker discovery and validation related to lung cancer screening and in CT image analysis. In pursuit of its aims, the CVC has access to samples from a multitude of cohorts for validation studies.